Tributylamine

Endpoint summary

Description of key information

The read-across substance tributylamine hydrochloride is rapidly and nearly completly absorbed after oral application. Excretion is mainly via urine (about 70%), to a minor extent via air (about 28%) and only small amounts are excreted via faeces (up to 4%). Chain hydroxylated and debutylated metabolites were identified in urine as well as the unchanged test item.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Additional information

Two studies (RL2) are available on the toxicokinetics and metabolism of the test compound.

In the Hoechst AG (1990a) study, Wistar rats were given a single oral dose of 50 mg radiolabeled tributylamine hydrochloride/kg body weight. The oral absorption was complete. Maximum blood levels were determined in males within 4-8 h post application, in females within 4-6 h after dosing. The elimination of the blood was biphasic with half lives of 5.0 and 65.4 h in females and 6.6 and 69.8 h in males, respectively. 27.8% of the administered dose was found in the expired air within 48 h, 69.4 % in the urine and 3.7 % in the faeces within 7 days (only male animals tested). The excretion was biphasic with half lives of 4.6 and 42.3 in urine and 6.4 h and 48.9 h in faeces, respectively. The highest concentrations of radioactivity were found in urinary bladder (0.73 µg equivalents/g), followed by retroperitoneal fat (0.61 µg equivalents/g), liver (0.48 µg equivalents/g), subcutaneous fat (0.46 µg equivalents/g), bones (0.43 µg equivalents/g) and lung (0.40 µg equivalents/g). The kidneys, brain, pancreas, gonads, and heart contained 0.4 -0.2 µg equivalents/g, stomach, skeletal muscle and smooth muscle few below 0.2 µg equivalents/g and the other tissues were at or below detection limit. 0.51 % was retained in the examined organs 1 week post application, the highest amount (0.2 %) was observed in the skeletal muscle. According to the authors these slight differences between the contents of organs indicate the metabolism of the test substance to endogenous substances, which are incorporated into the organism. The recovery of excreted material and radioactivity in the organs was complete.

In summary, Wistar rats received orally 50 mg TBA-HCl/kg bw. The substance contained a radiolabel: ^[14]C: Butyl*-N-(butyl)₂. The substance was rapidly absorbed, metabolised, and excreted. Excretion was complete, and only a small percentage of the administered dose remained in the carcass. Key findings are tabulated below.  

 

radioactivity in	% of dose (approx. means)
Air (= CO2)	28    (48 hrs)
urine	70   (48 hrs)
Faeces	4     (48 hrs)
Organs	0.5   (7days)
Organ distribution	Uniform and low (µg Eq./g tissue) (urinary baldder 0.73 retroperitoneal fat 0.61 Liver 0.48 Subcutaneous fat 0.46 Bone 0.43 Lung 0.4
	Sum: 104 +/-

 

In a second study (Hoechst AG, 1990b) the urinary metabolites from the above experiment were characterised. The unchanged test substance and the identified urinary metabolites accounted for approx. 86 % of the total radioactivity in urine. The unchanged test substance accounted for 10%; chain hydroxylation for 60%; and deamination to Di-n-butylamine derivatives for approx. 33% of the administered dose. 14% were unidentified. The table below gives details. (Hoechst, 1990b).

Metabolite In urine	% of dose (approx. means)
Butyl*-N-(butyl)2	10 (unchanged TS)
(Butyl)2-N-butyl-OH	25
Butyl-N-(butyl-OH)2	19
Butyl-NH-butyl-OH2	12.5
Butyl-NH-butyl	20
2 peaks unidentified	10 + 4

It is concluded that deamination is not the sole metabolic pathway, but the secondary amine is formed to approx. 33% from the tertiary amine which justifies a vertical read across between the tertiary amine and the respective secondary amine. Further, C-hydroxylation is a major pathway fur tri-n-butylamine. This is also expected to hold true for more lipophilic substituents with larger chain length.

Tributylamine is caustic and no information is available on dermal absorption.